L37
A Trial of an Oral CRTH2 Antagonist in Antihistamine-Refractory Chronic Spontaneous Urticaria
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Eric Oliver, MD, Kristin Chichester, MS, Kelly Devine, RN, Patricia M. Sterba, MS, Craig Wegner, PhD, Becky Vonakis, PhD FAAAAI, Sarbjit S. Saini, MD FAAAAI
Rationale:

Chronic spontaneous urticaria (CSU) skin lesions show degranulated mast cells and infiltration by CRTh2-bearing leukocytes. Our prior work demonstrated altered blood basophil and eosinophil surface CRTh2 expression in CSU. We sought to evaluate the safety and efficacy of the oral CRTh2 antagonist AZD1981 in CSU.

Methods:

Antihistamine-refractory adult CSU subjects were recruited for a Phase II study involving 4 weeks of double-blind, placebo-controlled treatment with AZD1981. Subjects completed daily hive and itch scoring and disease activity surveys. We examined PGD2-induced eosinophil shape change, blood total leukocyte histamine content, CBC differentials, and CRTh2 expression on blood basophils, eosinophils, and ILC2s at baseline and after treatment.

Results:

Thirty-six subjects were screened and 22 subjects completed the study. Weekly itch scores were significantly lower 1 week following active treatment with AZD1981 (9.5 to 7.2, n=12, p=.0264). PGD2-induced eosinophil shape change (10^-7 M PGD2) was significantly reduced at the end of treatment (26.9 to 5.1 net MFI, n=12, p=.0005) but was similar in the placebo group (10.44 to 7.81 MFI, n=8, p=.8438). CBC eosinophil percent significantly increased with active therapy (3.17% to 4.43%, n=12, p=.0396). No SAE’s were reported.

Conclusions:

This is the first study of an oral CRTh2 antagonist patients with antihistamine-refractory CSU. AZD1981 treatment led to reductions in patient reported itch, reduced PGD2-induced eosinophil shape change, increased basophil CRTh2 expression, and increased blood eosinophils in CSU subjects. These results provide evidence supporting the role for this pathway in CSU.